| Respiratory syncytial virus (RSV) is a pathogen of major clinical significance for infants, the elderly, and the immunocompromised. In BALE/c mice, primary infection with RSV is benign. However, if these mice are vaccinated with the attachment (G) glycoprotein of RSV and later infected with RSV, robust Th1 and Th2 responses, lymphocytic and eosinophilic infiltrates and enhanced injury occur in the lungs. This immunopathology is mediated by memory CD4 + T cells and mimics the responses seen in vaccinated infants upon subsequent natural infection during a disastrous failed vaccine trial for RSV in the 1960s. For a successful vaccine against RSV to be developed, the mistakes of the past must be avoided by a more thorough understanding of the memory CD4+ T cell response to this virus.; An examination of this response in the BALB/c mouse model has revealed several of its unique characteristics. The memory CD4+ T cell response to RSV G is directed against a single immunodominant epitope, to which both Th1 and Th2 cells respond. These T cells have an unexpectedly narrow Vbeta repertoire, and predominantly express Vbeta14 as part of their TCR. Using this Vbeta chain as a marker of the memory population, studies investigating the sites of activation, migration, proliferation, and differentiation of RSV-specific memory CD4+ T cells were undertaken.; Surprisingly, results of these studies suggest that following RSV infection of RSV G-primed mice, the potent CD4+ memory response in the lungs requires prior trafficking through lymphoid organs, which occurs very rapidly, rather than direct activation in the lungs. After passage through lymph nodes, the cells migrate to the infected lungs and undergo several rounds of division and simultaneous acquisition of effector functions.; The lungs, during active viral infection, are a source of abundant RSV antigens, and RSV infection has previously been shown to cause defects in the anti-viral function of memory RSV-specific CD8+ T cells. The model presented herein, in which memory CD4+ T cells complete differentiation in the lungs, amid plentiful viral antigens, provides a possible mechanism by which these anti-viral CD4+ T cells are modulated by RSV. |
